Three Decades Single Center Experience of Airway Complications After Lung Transplantation.

Post lung transplantation airway complications like necrosis, stenosis, malacia and dehiscence cause significant morbidity, and are most likely caused by post-operative hypo perfusion of the anastomosis. Treatment can be challenging, and airway stent placement can be necessary in severe cases. Risk factors for development of airway complications vary between studies. In this single center retrospective cohort study, all lung transplant recipients between November 1990 and September 2020 were analyzed and clinically relevant airway complications of the anastomosis or distal airways were identified and scored according to the ISHLT grading system. We studied potential risk factors for development of airway complications and evaluated the impact on survival. The treatment modalities were described. In 651 patients with 1,191 airway anastomoses, 63 patients developed 76 clinically relevant airway complications of the airway anastomoses or distal airways leading to an incidence of 6.4% of all anastomoses, mainly consisting of airway stenosis (67%). Development of airway complications significantly affects median survival in post lung transplant patients compared to patients without airway complication (101 months versus 136 months, p = 0.044). No significant risk factors for development of airway complication could be identified. Previously described risk factors could not be confirmed. Airway stents were required in 55% of the affected patients. Median survival is impaired by airway complications after lung transplantation. In our cohort, no significant risk factors for the development of airway complications could be identified.

Analysis of the relative deformation of lung lobes before and after surgery in patients with NSCLC.

An accurate assessment of the extent of the tumor is critical for successful local treatment of lung cancer by surgery and/or radiotherapy. Guidelines to establish the extent of treatment margins may be derived from correlation studies between pre-treatment imaging and histopathology. Deformations occur, however, between in-vivo CT imaging and ex-vivo pathology due to the softness of lung tissue and pathology processing. The first aim of this study was to quantify these deformations in tissue around non-small cell lung cancer. The second aim was to explore factors associated with the magnitude of the deformations. The study was performed in 25 patients who underwent lobectomy after preoperative CT. Non-rigid registration was employed to evaluate tissue deformations around the gross tumor volume (GTV), taking into account potential differences in elasticity between tumor and healthy lung tissue. Tissue was found to be compacted by approximately 60% depending on circularity of the tumor and orientation of the specimen on the pathology table during processing. The deformations give rise to potential underestimation of the treatment margins in pathology studies that do not take this aspect into account.

[Guideline 'Differentiated thyroid carcinoma', including diagnosis of thyroid nodules]. / Richtlijn 'Gedifferentieerd schildkliercarcinoom', inclusief de diagnostiek van de schildkliernodus.

Differentiated thyroid carcinoma is a rare disease. Appropriate diagnosis, treatment and follow-up are complex but greatly influence treatment outcomes and patient quality of life. Patients with differentiated thyroid carcinoma present in many hospitals throughout the Netherlands, underscoring the need for uniformity in diagnosis and treatment. This prompted the Dutch Society of Nuclear Medicine and the Dutch Endocrine Society to develop an evidence-based guideline that emphasises not only new scientific developments but also the organisation of care. Thyroid-stimulating hormone (TSH) assessment and fine needle aspiration cytology play a central role in the diagnostic assessment of a patient with a thyroid nodule. Ablation of residual thyroid tissue with radioiodine (1-131) is recommended for all patients who have undergone total thyroidectomy. Follow-up protocols distinguish between patients with a low risk of thyroid-carcinoma recurrence and those with a non-low risk of recurrence.

Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group.

OBJECTIVE: The survival benefit of adjuvant radiotherapy and 5-fluorouracil versus observation alone after surgery was investigated in patients with pancreatic head and periampullary cancers. SUMMARY BACKGROUND DATA: A previous study of adjuvant radiotherapy and chemotherapy in these cancers by the Gastrointestinal Tract Cancer Cooperative Group of EORTC has been followed by other studies with conflicting results. METHODS: Eligible patients with T1-2N0-1aM0 pancreatic head or T1-3N0-1aM0 periampullary cancer and histologically proven adenocarcinoma were randomized after resection. RESULTS: Between 1987 and 1995, 218 patients were randomized (108 patients in the observation group, 110 patients in the treatment group). Eleven patients were ineligible (five in the observation group and six in the treatment group). Baseline characteristics were comparable between the two groups. One hundred fourteen patients (55%) had pancreatic cancer (54 in the observation group and 60 in the treatment group). In the treatment arm, 21 patients (20%) received no treatment because of postoperative complications or patient refusal. In the treatment group, only minor toxicity was observed. The median duration of survival was 19.0 months for the observation group and 24.5 months in the treatment group (log-rank, p = 0.208). The 2-year survival estimates were 41% and 51 %, respectively. The results when stratifying for tumor location showed a 2-year survival rate of 26% in the observation group and 34% in the treatment group (log-rank, p = 0.099) in pancreatic head cancer; in periampullary cancer, the 2-year survival rate was 63% in the observation group and 67% in the treatment group (log-rank, p = 0.737). No reduction of locoregional recurrence rates was apparent in the groups. CONCLUSIONS: Adjuvant radiotherapy in combination with 5-fluorouracil is safe and well tolerated. However, the benefit in this study was small; routine use of adjuvant chemoradiotherapy is not warranted as standard treatment in cancer of the head of the pancreas or periampullary region.

Histological determinants for different types of local recurrence after breast-conserving therapy of invasive breast cancer. Dutch Study Group on local Recurrence after Breast Conservation (BORST)

The purpose of this study was to determine which histological factors are associated with an increased risk for local recurrence in the breast after breast-conserving therapy for early breast cancer (TNM stage I and II) and whether risk patterns vary according to menopausal status and type of local recurrence. Through complete follow-up of the patients of eight regional radiation oncology departments, two cancer institutes and one surgical clinic in The Netherlands, 360 patients were identified with local recurrence in the breast after having received breast-conserving therapy (local tumour excision, axillary dissection and irradiation of the whole breast and a boost to the tumour bed) during the 1980s. For each case, two controls with a follow-up of similar duration without local recurrence were randomly selected. Histological slides of the primary tumour were reviewed. Among premenopausal patients the risk of recurrence for those younger than 35 years was significantly higher than that for premenopausal patients of 45 years or older (relative risk (RR) 2.9; 95% confidence interval (95% CI) 1.3-6.6, P < 0.05). The risk of recurrence at or near the site of the primary tumour was most significantly increased for patients with high grade extensive intraductal component (EIC) adjacent to the primary tumour (RR 4.1; 95% CI 1.7-9.8, P < 0.01). Microscopic margin involvement was an important risk indicator for diffuse recurrence and recurrence in the skin of the breast, especially in the presence of vascular invasion (RR 25; 95% CI 4.0-150, P < 0.001). To prevent local recurrence at or near the site of the primary tumour, local excision with a 1-2 cm margin of healthy tissue and a 15 Gy boost seemed adequate local treatment for patients with well differentiated EIC. In contrast, a wider surgical margin, a higher boost dose or mastectomy should be considered for patients with poorly differentiated EIC. Microscopic margin involvement in the presence of vascular invasion significantly increases the risk of diffuse recurrence or recurrence in the skin.

Which cytological criteria are the most discriminative to distinguish carcinoma, lymphoma, and soft-tissue sarcoma? A probabilistic approach.

The reliability of fine-needle aspiration cytology (FNA) for distinguishing between carcinoma, lymphoma, and sarcoma was established in a previous study (Thunnissen et al., Cytopathology 1993; 4:107-114). The purpose of this study was to investigate which criteria were useful for a probabilistic diagnosis. A total of 78 randomly chosen FNA smears (31 carcinomas, 24 lymphomas, and 23 sarcomas) was sent around and read "blindly" by six cytopathologists. Each pathologist completed a list of 16 criteria for every case. Histology was used as a reference standard. A statistical analysis led to the selection of three criteria: "lymphoglandular bodies," "well-defined clusters," and "spindle-cell nuclei," associated with lymphoma, carcinoma, and soft-tissue sarcoma, respectively. Given the scores on these criteria, the probabilities to be assigned to the three diagnostic categories can be read from a table. It turns out, as one might expect, that the classification of the most probable disease is pretty reliable if one cytologic criterion scores much higher than the other two criteria. On other cases, fuzziness appears and misclassifications are far from improbable. This study offers a general cytologic approach. The cytologic criteria "lymphoglandular bodies," "well-defined clusters," and "spindle-cell nuclei" can be used both in daily practice and in education to assign posterior probabilities to carcinoma, lymphoma, and soft-tissue sarcoma.

Stable-Isotope Analysis of a Combined Nitrification-Denitrification Sustained by Thermophilic Methanotrophs under Low-Oxygen Conditions.

To simulate growth conditions experienced by microbiota at O(inf2)-limited interfaces of organic matter in compost, an experimental system capable of maintaining dual limitations of oxygen and carbon for extended periods, i.e., a pO(inf2)-auxostat, has been used. (sup15)N tracer studies on thermophilic (53(deg)C) decomposition processes occurring in manure-straw aggregates showed the emission of dinitrogen gas from the reactor as a result of simultaneous nitrification and denitrification at low pO(inf2) values (0.1 to 2.0%, vol/vol). The N loss was confirmed by nitrogen budget studies of the system. Depending on the imposed pO(inf2), 0.6 to 1.4 mmol of N/day (i.e., 20 to 40% of input N) was emitted as N(inf2). When the pO(inf2) was raised, the rates of both nitrification and denitrification increased instantaneously, indicating that ammonia oxidation was limited by oxygen. In auxostats permanently running at pO(inf2) >= 2% (vol/vol), the free ammonium pool was almost completely oxidized and was converted to nitrite plus nitrate and N(inf2) gas. Labelling of the auxostat with [(sup13)C]carbonate was conducted to reveal whether nitrification was of autotrophic or heterotrophic origin. Incorporation of (sup13)CO(inf2) into population-specific cellular compounds was evaluated by profiling the saponifiable phospholipid fatty acids (FAs) by using capillary gas chromatography and subsequently analyzing the (sup13)C/(sup12)C ratios of the individual FAs, after their combustion to CO(inf2), by isotope ratio mass spectrometry. Apart from the observed label incorporation into FAs originating from a microflora belonging to the genus Methylococcus (type X group), supporting nitrification of a methylotrophic nature, this analysis also corroborated the absence of truly autotrophic nitrifying populations. Nevertheless, the extent to which ammonia oxidation continued to exist in this thermophilic community suggested that a major energy gain could be associated with it.

Mammographic and sonographic spectrum of non-puerperal mastitis.

The goal of this study was to explore possible specific mammographic and sonographic features in women with non-puerperal mastitis (NPM), in order to make an accurate diagnosis and prevent unnecessary surgical procedures. From a group of 93 patients with NPM diagnosed between 1987 and 1992, the mammograms of 41, the sonograms and cytology of 47, and the histology of seven patients were retrospectively reviewed. Follow-up was performed on those without histology. In 20 of the 47 patients the inflammation was located subareolarly. In 50% of those with non-subareolar lesions, mammography showed a circumscribed lesion. Sonographically, all patients had an identifiable lesion either well or poorly defined. The majority of the lesions were cystic, but in 23 of 47 cases solid components were seen. Signs of infection in cystic lesions were observed in 25 of 47 cases. Posterior shadowing was not observed. During the follow-up period no breast malignancy was found. It is concluded that NPM has no specific mammographic or sonographic sign. Diagnosis should be made with additional diagnostic assessment, such as FNAB, which was diagnostic in all cases.

Somatostatin-receptor scintigraphy in primary breast cancer.

Somatostatin-receptor (SS-R) scintigraphy successfully shows primary cancers and distant metastases in most patients with carcinoids, islet cells tumours, and paragangliomas. Previous in-vitro studies indicated that somatostatin receptors are present in human breast cancers. We report positive scintigraphy with [111In-DTPA-D-Phe1]-octreotide in 39 of 52 primary breast cancers (75%). Parallel in-vitro autoradiography with [125I-Tyr3]-octreotide of 30 of these showed a corresponding somatostatin-receptor status in 28. Significantly more invasive ductal cancers could be shown than invasive lobular carcinomas (85% vs 56%; p < 0.05). Also the number of T2 cancers which were shown was higher than T1 (86% vs 61%; p < 0.05). Imaging of the axillae showed non-palpable cancer-containing lymph nodes in 4 of 13 patients with subsequently histologically-proven metastases. In the follow-up after a mean of 2.5 yr, SS-R scintigraphy in 28 of the 37 patients with an originally SS-R-positive cancer, was positive in the 2 patients with clinically-recognised metastases, as well as in 6 of the remaining 26 patients who were symptom-free. Raised carcinoembryonic antigen (CEA) and CA 15-3 values were observed in only 2 and 1, respectively, of these patients. Most primary breast cancers can be shown by SS-R scintigraphy, especially invasive ductal cancers. This technique may be of value in selecting patients for clinical trials with somatostatin analogues or other medical treatments. Furthermore, SS-R scintigraphy is more sensitive than measurements of the usual serum cancer markers for detecting recurrences of SS-R-positive breast cancer.

CT assessment of resectability prior to transhiatal esophagectomy for esophageal/gastroesophageal junction carcinoma.

The ability of preoperative CT to assess resectability and to stage carcinoma of the esophagus and gastroesophageal junction was studied in 71 patients who underwent transhiatal esophagectomy. Patients with preoperatively proven distant metastases who did not have surgery were not included in the present study. At surgery the tumor invaded adjacent mediastinal or abdominal structures in 18 patients (prevalence 25%), but was nonresectable in only 7 of these 18 patients (39%). Invasions of the tracheobronchial tree, the aorta, and the diaphragm were correctly detected on CT in 5 of 6, 1 of 2, and 2 of 10 patients. There were four false-positive results on CT; tracheobronchial invasion and pericardial invasion were incorrectly predicted in one and three patients, respectively. Invasion of adjacent structures was correctly assessed on CT in 58 (82%) patients and the depth of tumor invasion was correctly determined in 49 (69%) patients. Computed tomography correctly staged 57% of patients according to the classification of the American Joint Committee on Cancer. Understaging (31%) occurred more often than overstaging (11%). In the present study, computed tomography was not effective in assessing non-resectability by diagnosing invasion because of the relatively low prevalence of invasion of adjacent structures and the fact that invasion was often not associated with nonresectability. In assessing invasion itself, CT was accurate in diagnosing tracheobronchial involvement, but was limited in diagnosing invasion of other adjacent structures. In assessing stage grouping, CT was limited in detecting either diaphragmatic invasion or lymph node involvement.

Somatostatin receptor-positive primary breast tumors: genetic, patient and tumor characteristics.

In a series of 87 primary breast tumors, somatostatin receptor (SSR) expression was detected by in vitro autoradiography in 58 tumors. In 41 tumors the SSR expression was homogeneous and in 17 it was heterogeneous. Although the tumors were not selected by the investigators upon entry in the study, examination of the tumor and patient characteristics showed that a pre-selection had taken place for small tumors. Eighty percent of the tumors were classified as stage pT1 or pT2 tumors. This small tumor size and the large size of the tumor sections used for autoradiography can explain the high incidence of somatostatin expression in our series. Forty-three of these tumors, 30 SSR-positive and 13 SSR-negative, were tested for morphological and (immuno)histochemical markers of neuroendocrine differentiation. Three SSR-positive tumors were also positive for 2 or more other markers of neuroendocrine differentiation, suggesting that neuroendocrine breast tumors and SSR-positive breast tumors are overlapping, but independent, subgroups of tumors. To test whether specific genetic alterations are associated with SSR-positive or SSR-negative breast tumors, we examined in a selected series of 47 SSR-positive and 32 SSR-negative breast tumors a number of known genetic markers by Southern blotting. Deletions or rearrangements of the retinoblastoma (RB) tumor-suppressor gene were observed in 5 SSR-positive and 5 SSR-negative tumors. In 4 SSR-positive and also in 4 SSR-negative tumors an amplification of the neu oncogene was observed. Amplifications of the int-2 oncogene were found in 2 SSR-positive and 1 SSR-negative breast tumor. In one SSR-positive tumor an amplification of the c-myc oncogene was observed and in another SSR-positive tumor a rearrangement of the L-myc oncogene was found.

Improved assessment of supraclavicular and abdominal metastases in oesophageal and gastro-oesophageal junction carcinoma with the combination of ultrasound and computed tomography.

The purpose of the study was to evaluate ultrasound and computed tomography in the assessment of distant metastases, supraclavicular and abdominal, in 113 patients with carcinoma of the oesophagus and gastrooesophageal junction. Ultrasound and computed tomographic findings were compared with the cytological data in 29 patients and with the surgical data in 84 patients. In assessing distant metastases, ultrasound and computed tomography had a sensitivity of 61% and 70%, and a specificity of 93% and 85%, respectively (p = 1.0). When ultrasound and computed tomography were combined the sensitivity increased to 83% and the specificity decreased to 81%. There was no significant difference in the assessment of supraclavicular metastases (p = 0.8), coeliac metastases (p = 1.0) or liver and other non-lymphatic abdominal metastases (p = 1.0) on ultrasound or computed tomography. The results show that both ultrasound and computed tomography should be used for assessment of distant metastases and abnormalities confirmed by image-guided biopsy.

Reliability of fine needle aspiration cytology for distinguishing between carcinoma, lymphoma and sarcoma; the influence of clinical information.

To investigate interobserver variation of fine needle aspiration (FNA) cytological diagnosis with respect to distinguishing between carcinoma, sarcoma and lymphoma, a set of 80 randomly sampled slides was randomized twice and read 'blindly' by five cytopathologists. In the first round the slides were read without any information, and in the second round clinical information was provided. Histology was used as a reference standard. In the first round, the positive predictive values for the cytological diagnosis of carcinoma, sarcoma and lymphoma were 93%, 94% and 86% respectively. In the second round the positive predictive values for the cytological diagnoses of carcinoma, sarcoma and lymphoma were 95%, 99% and 99%, respectively. Interobserver variability, tested with weighted kappa scores (range 0.73-0.92) between histological and cytological diagnosis, was low. The most accurate FNA cytologic classification was obtained when the clinical context was known.

The advantages of pylorus-preserving pancreatoduodenectomy in malignant disease of the pancreas and periampullary region.

The aim of this study was to establish whether the pylorus-preserving pancreatoduodenectomy (PPPD) is a safe and radical procedure in malignant disease of the head of the pancreas and periampullary region, without increased morbidity and mortality rates compared with the standard Whipple's procedure. During the period 1984 to 1990, a Whipple's procedure (n = 44) or PPPD (n = 47) was performed in 91 patient. In-hospital mortality rates were 2% after PPPD and 5% after Whipple's procedure. Median duration of the resection procedure and median blood loss in the PPPD group were 210 minutes and 1800 mL, respectively. After Whipple's procedure, these figures were 255 minutes and 2500 mL, both significantly different (p less than 0.01) as compared with PPPD. No difference was found during follow-up with respect to days of gastric suctioning, start of liquid diet, normal diet, complaints of ulcer disease, postoperative complications, recurrence of disease, and survival. In all patients, curative resection was performed with comparable TNM (tumor, nodes, metastases) staging. The number of tumor-containing duodenal or gastric resection margins did not differ in both groups of patients (two patients after PPPD, two patients after Whipple's procedure). Hospital stay was significantly (p = 0.02) shorter after PPPD; median 14 days, compared with median 18 days after Whipple's procedure. The advantage of the PPPD is that it is an easier and less time-consuming operation, with less blood loss, a shorter hospital stay, and better weight gain (p = 0.02) during follow-up. In conclusion, PPPD is a safe and radical procedure for cancer in the head of the pancreas or periampullary region, with the same survival and appearance of locoregional recurrence and distant metastases as after standard Whipple's resection.

Assessment of distant metastases with ultrasound-guided fine-needle aspiration biopsy and cytologic study in carcinoma of the esophagus and gastroesophageal junction.

The use of ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) for the assessment of distant metastases was prospectively studied in 135 consecutive patients with carcinoma of the esophagus and gastroesophageal junction. Patients with accessible lesions on US and computed tomographic (CT) studies of the supraclavicular regions and the abdomen underwent US-guided FNAB. In patients with multiple lesions biopsies were preferentially performed on enlarged supraclavicular nodes. Forty-nine patients underwent US-guided FNABs of 53 lesions. A cytologic diagnosis was established in 46 of 53 (87%) biopsies. Seven of 53 (13%) biopsies were nondiagnostic. Distant metastases were diagnosed by means of cytologic study in 33 of 135 (24%) patients. Supraclavicular metastases were diagnosed in 22 patients and abdominal metastases were diagnosed in 12 patients, including one patient who also had supraclavicular metastases. US-guided FNAB can improve the selection of patients for surgical and nonsurgical treatment by diagnosing distant metastases in an important number of patients.

Supraclavicular lymph node metastases in carcinoma of the esophagus and gastroesophageal junction: assessment with CT, US, and US-guided fine-needle aspiration biopsy.

The preoperative assessment of supraclavicular lymph node metastases was prospectively studied in 100 patients with carcinoma of the esophagus and gastroesophageal junction. Findings at computed tomography (CT), ultrasound (US), and palpation were compared, and US-guided fine-needle aspiration biopsy of nodes with a small axis of 5 mm or greater was performed. Supraclavicular metastases were detected on CT scans in 11 of 13 patients (85%) and on US scans in 14 of 16 patients (88%) but were palpable in only three of the 16 patients (19%). The predictive value of a supraclavicular node indicating metastases was .74 at US and .85 at CT. Metastases were diagnosed in 10 of 46 patients with squamous cell carcinoma (22%) and five of 50 patients (10%) with adenocarcinoma. Nodes with metastases had a round configuration, with a statistically significant greater short-axis to long-axis ratio than that of benign nodes (0.89 vs 0.54; P = .05). In four of 16 patients (25%) with supraclavicular metastases proved with cytologic examination, neither CT nor US of the mediastinum and abdomen showed enlarged nodes.

Ultrasound and ultrasound-guided fine needle aspiration biopsy of supraclavicular lymph nodes in patients with esophageal carcinoma.

The use of ultrasound combined with ultrasound-guided fine-needle aspiration biopsy (UGFAB) of supraclavicular lymph nodes in the pretreatment staging of 37 patients with squamous cell carcinoma of the esophagus is described. All patients underwent computed tomography (CT) scans of the chest and the abdomen and ultrasound of the abdomen and supraclavicular regions. Supraclavicular lymph node metastases (Stage IV disease according to the tumor nodes metastasis [TNM] classification) were cytologically diagnosed in seven (18.9%) of the 37 patients. In two of these patients, no other metastases were found. In the other five patients, UGFAB replaced more invasive diagnostic procedures. Due to their superficial location, ultrasound and UGFAB of the supraclavicular lymph nodes was relatively simple to perform, and contributed to an improved staging of squamous cell carcinoma of the esophagus.

Comparison of the chitinolytic properties of Clostridium sp. strain 9.1 and a chitin-degrading bacterium from the intestinal tract of the plaice, Pleuronectes platessa (L.).

The chitinolytic properties of a facultatively anaerobic bacterium isolated from the hindgut of plaice were compared with those of Clostridium sp. strain 9.1, a bacterium isolated from anoxic estuarine sediment. The chitinolytic enzyme systems of the gut isolate and strain 9.1 both released N,N'-diacetylchitobiose (NAG2) as the major hydrolysis end-product. During the hydrolysis of chitin, there was transient accumulation of a non-sedimentary chitin fraction which was not detectable by high-performance liquid chromatography. Growth on NAG2 repressed chitinase synthesis in the gut isolate but not in the Clostridium species. Thiol reagents were strongly inhibitory to the chitinase of the strict anaerobe but did not affect the hydrolytic enzymes of the gut isolate. When the two bacteria were cocultured with chitin as the sole carbon and energy source, Clostridium sp. strain 9.1 was always outcompeted. Experiments with batch and phauxostat cultures showed that the competitiveness of strain 9.1 could be improved dramatically by the inclusion in the cocultures of a non-chitinolytic bacterium capable of fermenting chitin oligomers. The cooperation between the oligomer-fermenting species and the Clostridium sp. is discussed in relation to the regulation of chitinolytic activity in the latter organism.

Acute polyhydramnios associated with fetal hepatoblastoma.

A 28-yr-old gravida II mother presented at 29 wk gestation with acute polyhydramnios. The most common causes for polyhydramnios were excluded and onset of preterm labor at 31 wk prevented further studies. Tocolysis failed and a severely asphyxiated boy was born. He had a very distended abdomen with a 7 cm hepatomegaly and was in shock. No other physical abnormalities were found. The child died 15 min after birth. At post mortem examination a fetal type hepatoblastoma was detected. Duodenal obstruction due to the liver tumor might have caused the polyhydramnios.