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.

Leukocyte myeloperoxidase deficiency and diabetes mellitus associated with Candida albicans liver abscess.

Reported here is a case of hereditary myeloperoxidase deficinecy in a diabetic patient suffering from a Candida albicans liver abscess. Peroxidase activity is completely absent from the neutrophils and monocytes although it is present in the eosinophils. The different forms of myeloperoxidase deficiency are discussed.

Surgery for chronic pancreatitis.

We operated on 102 patients (89 men and 13 women) who had chronic pancreatitis. The mean age at the time of surgery was 45 1/2 years. Of these patients, 77 had resections (57 distal pancreatectomies, 17 duodenopancreatectomies, an three total pancreatectomies) and 25 had diversion procedures (15 Puestow operations and 10 internal drainage of cysts). The indication for surgery was abdominal pain in 88% and the presence of jaundice in 21%. Our patients had severe pancreatic disease: 64% had pseudocysts, 41% had calcifications, and 26% had calculi in the duct of Wirsung. The postoperative mortality rate was low (3%), but morbidity occurred in 18% (mostly after resection procedures). The incidence of diabetes after surgery was high after resection (57%) but it also occurred after diversion procedures (10%). The quality and length of survival was similar after resections and after diversions, although patients with alcoholic pancreatitis had the worst long-term prognosis. Reoperations were performed in 16% of all patients; the incidence was lower after duodenopancreatectomy.

Surgical treatment of hydatid disease of the liver: a survey of 69 patients.

Sixty-nine patients were operated on because of hydatid disease of the liver from 1960 to 1986. There were 32 male and 37 female patients, with a mean age of 38 years at operation (range, 13 to 76 years). Forty-two cysts were solitary, 20 multiple, and 7 bilateral; 45 were located in the left lobe. Radical surgical procedures were carried out in 45 patients and consisted of cystectomy in six, pericystectomy in 25, and hepatectomy in 14; a conservative approach was used in 11 (resection of prominent part, internal or external drainage). The remaining 13 patients underwent a combination of both techniques. There were no deaths. Postoperative morbidity was low and equally distributed whether surgery was radical or conservative. Local complications occurred in six patients (9%), and seven other patients (10%) had systemic disorders. Four patients required reoperation: two for hemostasis and two for persistent fistulae (one biliary and one bronchobiliary). Of the 42 patients available for follow-up (61%), four (9%) had recurrent disease. One had undergone a pericystectomy and three, conservative procedures, at the time of primary surgery. Our results support the view that excisional surgery is a safe and valid option for patients with hydatid liver disease.

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.

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.

Postoperative pulmonary embolism after hospital discharge. An underestimated risk.

During a 10-year period (1980 through 1989), 28,953 patients were admitted to our Clinic of Digestive Surgery, Geneva, Switzerland. Two thirds of them were operated on, and one third were treated conservatively. Symptomatic pulmonary embolism (PE) was recorded in 90 patients (0.31%; 95% confidence interval, 0.25% to 0.38%) during their hospital stay. Within 30 days of hospital discharge, 29 patients were readmitted because of PE (incidence of delayed PE, 0.10%; 95% confidence interval, 0.07% to 0.14%; total incidence of PE, 0.41%; 95% confidence interval, 0.34% to 0.49%). In the operated-on group, the delayed embolic events occurred a median of 6 days (range, 2 to 25 days) after discharge and 18 days (range, 6 to 35 days) after surgery. Delayed PEs were more frequent after so-called low-risk surgery. Thus, the rate of postoperative PE increased by 30% when PEs occurring within 30 days of hospital discharge were considered, and this provides a useful basis for prolonged prophylactic measures after hospital stay.

Results of operative treatment of gastrointestinal tract tumors in patients over 80 years of age.

Between 1981 and 1986, 140 patients over 80 years of age were operated on for a gastrointestinal tract tumor in our service. There were 24 gastric, one small-bowel, 91 colonic, and 24 rectal cancers. Only 40% of the patients were preoperatively free of any systemic disorder other than tumor. We performed surgical procedures with a curative intent for 90 (64%) of them. Our mean overall postoperative mortality was 17%, but this rate could be decreased by performing elective operations on well-prepared patients. Over 80% of the deaths were related to systemic organ failures. Eighty-three percent of the survivors (96 patients) returned to their homes; 82% (94 patients) had normal activities for their age. The actuarial survival curve showed a 50% survival rate at three years, all tumoral stages included. These results support the view that surgery is a safe, valid option in the face of gastrointestinal tract tumors in the elderly.

Unexpectedly high rate of phlebographic deep venous thrombosis following elective general abdominal surgery among patients given prophylaxis with low-molecular-weight heparin.

One hundred ninety-four patients undergoing elective general abdominal surgery were randomized in a single-blind study to receive one daily subcutaneous injection of a low-molecular-weight heparin, dalteparin sodium (2500 IU, n = 97) or nadroparin calcium (3075 IU, n = 97), two regimens that are approved in Europe to prevent deep venous thrombosis. On the eight postoperative day, bilateral ascending leg phlebography (n = 185) showed the presence of deep venous thrombosis in 45 cases (24.3%; 95% confidence interval, 18% to 31%), with a significantly higher rate (on intention-to-treat) among the patients who received the lower dosage (30 vs 15 deep venous thromboses). We conclude that the two regimens of low-molecular-weight heparin that were used in this study failed to prevent postoperative phlebographically proved deep venous thrombosis in one of four patients.

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.

Determination of pancreatic carboxypeptidase A in human blood serum.

A method has been designed for the assay of pancreatic carboxypeptidase A in blood serum. It uses Z-Gly-Phe as the substrate and fluorimetric determination of the released phenylalanine in an amino acid analyser, which yields a measure of free carboxypeptidase A. In addition, the sum (free carboxypeptidase A + procarboxypeptidase A) can be determined on a second portion preincubated with trypsin, which converts the proenzyme to the active form. Determinations made in fifteen healthy individuals showed the presence of a measurable concentration of free carboxypeptidase A. In acute pancreatitis, total carboxypeptidase A is raised. An increase in circulating proenzyme is observed in some cases. Data from 46 patients show a good correlation between total carboxypeptidase A, lipase and immunoreactive trypsin. Differential determination of procarboxypeptidase A and free carboxypeptidase A provides an interesting new tool for the diagnosis of pancreatic disorders.

Increase of creatine kinase and lactate dehydrogenase in the serum of rats submitted to experimental intestinal infarction.

Acute intestinal ischemia is a severe condition for which no early biochemical index exists at present. We have investigated the effect of experimental intestinal infarction in the rat on the serum concentration of total creatine kinase, creatine kinase BB and total lactate dehydrogenase. Suppression of blood supply from the superior mesenteric artery resulted in marked increases of total creatine kinase, of its BB isoenzyme, and of total lactate dehydrogenase. Whereas total creatine kinase and total lactate dehydrogenase cannot be regarded as specific markers of the intestine, creatine kinase BB could prove to be more specific in view of its limited tissue distribution.

Value of contrast-enhanced computerized tomography in the early diagnosis and prognosis of acute pancreatitis. A prospective study of 202 patients.

Two hundred two patients admitted with the clinical suspicion of acute pancreatitis underwent computerized tomography scanning within 36 hours of admission. The diagnostic value of the computerized tomography findings was excellent, with a sensitivity of 92 percent and a specificity of 100 percent. One hundred seventy-six patients with acute pancreatitis defined according to the overall clinical course were included in the prognostic study. The pancreatitis was fatal in 21 patients, severe in 47 patients, and mild in 108 patients. The computerized tomography findings were classified into the following three groups on the basis of the extent of phlegmonous extrapancreatic spread: Group I, no phlegmonous extrapancreatic spread (100 patients, none died); Group II, phlegmonous extrapancreatic spread in one or two areas (28 patients, mortality rate 4 percent); and Group III, phlegmonous extrapancreatic spread in three or more areas (48 patients, mortality rate 42 percent) (p less than 0.0001). The following three scores from prognostic clinical and laboratory data were also obtained: Score 1, zero or one positive sign (82 patients, none died); Score 2, two to four positive signs (54 patients, mortality rate 13 percent); Score 3, five or more positive signs (40 patients, mortality rate 35 percent) (p less than 0.001). The combination of computerized tomography findings and prognostic signs had the best predictive value. Patients in Group III, Score 3 (24 patients) or Group III, Score 2 (19 patients) had mortality rates of 58 percent and 32 percent, respectively, and complications developed in all of the survivors. In addition, all except two acute pancreatitis patients in whom pancreatic abscess developed were found in Group III (p less than 0.0001). Furthermore, for Group III patients, the prediction of death associated with abscesses was enhanced by the number of prognostic signs. The mortality rate increased from 17 percent for Score 2 patients to 81 percent for Score 3 patients (p = 0.0078). As a result of this study, we recommend early computerized tomography for all Score 2 and Score 3 patients, since it allows prompt recognition of patients at high risk for systemic and local complications. Adequate therapy can then be directed to the group of patients to whom it is best suited. Serial computerized tomographies should be reserved for those patients presenting with phlegmonous extrapancreatic spread.

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.

Conservative treatment of acute pancreatitis.

Most attacks of acute pancreatitis) have a favorable course and can thus be treated by conservative measures. The purpose of this review is: a) to present techniques (prognostic scores, computerized axial tomography, etc.) which can assist in the early identification of those cases of acute pancreatitis which can reasonably be submitted to non-surgical treatment; b) to summarize and discuss the main results of recent pharmaceutical research, and various conservative measures which have proven helpful in the treatment of this difficult disease.

[Pneumomediastinum and subcutaneous cervical emphysema as signs of rectosigmoid perforation]. / Pneumomédiastin et emphysème sous-cutané cervical témoins d'une perforation recto-sigmoïdienne.

Pneumomediastinum and subcutaneous emphysema of the neck occur exceptionally in spontaneous, retroperitoneal perforation of the sigmoid colon. These signs, in association with a septic syndrome and multiple organ failure, mandate the search of a gastrointestinal tract perforation, even in the absence of digestive symptoms. Careful deep palpation of the abdomen may determine the abdominal origin of the septic focus and thereby provide justification for exploratory laparotomy without further diagnostic investigations.

[Perforated tubular duplication of the sigmoid colon in adults]. / Perforation d'une duplication tubulaire sigmoïdienne chez l'adulte.

Intestinal duplications are rare malformations and a diagnostic challenge. The case presented herein relates to a perforated tubular duplication of the sigmoid colon in a 23-year-old man with intermittent abdominal pain during 3 months and a bout of peritonitis which resolved spontaneously. This case is unusual since duplications generally spare adults, are seldom found in the colon, and do not perforate. The only cases of duplication which can be suspected preoperatively belong to the communicating type or those containing ectopic gastric mucosa. The intraoperative finding in this case of a malformative mesenteric cyst reminds us that duplications can be found in association with other intestinal, vertebral, or genitourinary tract malformations. In conclusion, intestinal duplications should be resected even when they are asymptomatic, as occasional cancerous transformation associated with a poor prognosis have been reported.

[Acute Budd-Chiari's syndrome after surgical treatment of polycystic liver disease]. / Syndrome aigu de Budd-Chiari après traitement chirurgical d'une polykystose hépatique.

A case of acute Budd-Chiari syndrome after surgical treatment of polycystic liver disease is described. This complication, presently unreported in the literature, was secondary to the operative interruption of two hepatic veins, while the third was already obstructed by pericystic fibrosis. Preoperative radiologic vascular mapping should be performed in case of voluminous polycystic liver disease when associated liver resection appears likely.

[Resurgence of a forgotten pathology: pylephlebitis caused by tuberculous adenopathies]. / Résurgence d'une pathologie oubliée: la pyléphlébite par adénopathies tuberculeuses.

The incidence of abdominal tuberculosis represents less than 1% of all forms of tuberculosis. We report the case of a portal vein thrombosis associated with tuberculous adenopathy of the hepatic hilum discovered in a young woman free of symptoms, without any risk factors, who had recovered from a cavity pulmonary tuberculosis after a classical anti-tuberculous treatment. This case suggests that abdominal tuberculosis often remains undiagnosed. Reemergence of tuberculosis is likely because of the increase in the incidence of the acquired immunodeficiency syndrome.